Tumor-associated MΦ play a central role in lung cancer growth and metastasis, with bidirectional cross-talk between MΦ and cancer cells via CCR2 and CX3CR1 signaling as a central underlying mechanism. These findings suggest that the therapeutic strategy of blocking CCR2 and CX3CR1 may prove beneficial for halting lung cancer progression.

ROS are implicated in bone diseases. NADPH oxidase 4 (NOX4), a constitutively active enzymatic source of ROS, may contribute to the development of such disorders. Therefore, we studied the role of NOX4 in bone homeostasis. Nox4(-/-) mice displayed higher bone density and reduced numbers and markers of osteoclasts. Ex vivo, differentiation of monocytes into osteoclasts with RANKL and M-CSF induced Nox4 expression. Loss of NOX4 activity attenuated osteoclastogenesis, which was accompanied by impaired activation of RANKL-induced NFATc1 and c-JUN. In an in vivo model of murine ovariectomy–induced osteoporosis, pharmacological inhibition or acute genetic knockdown of Nox4 mitigated loss of trabecular bone. Human bone obtained from patients with increased osteoclast activity exhibited increased NOX4 expression. Moreover, a SNP of NOX4 was associated with elevated circulating markers of bone turnover and reduced bone density in women. Thus, NOX4 is involved in bone loss and represents a potential therapeutic target for the treatment of osteoporosis.

Background: Cat breeders observed a frequent occurrence of internal hydrocephalus in Persian cats with extreme brachycephalic head morphology.Objective: To investigate a possible relationship among the grade of brachycephaly, ventricular dilatation, and skull dysmorphologies in Persian cats.Animals: 92 Persian-, 10 Domestic shorthair cats. Methods: The grade of brachycephaly was determined on skull models based on CT datasets. Cranial measurements were examined with regard to a possible correlation with relative ventricular volume, and cranial capacity. Persians with high (peke-face Persians) and lower grades of brachycephaly (doll-face Persians) were investigated for the presence of skull dysmorphologies.Results: The mean cranial index of the peke-face Persians (0.97 AE 0.14) was significantly higher than the mean cranial index of doll-face Persians (0.66 AE 0.04; P < 0.001). Peke-face Persians had a lower relative nasal bone length (0.15 AE 0.04) compared to doll-face (0.29 AE 0.08; P < 0.001). The endocranial volume was significantly lower in doll-face than peke-face Persians (89.6 AE 1.27% versus 91.76 AE 2.07%; P < 0.001). The cranial index was significantly correlated with this variable (Spearman's r: 0.7; P < 0.0001). Mean ventricle: Brain ratio of the peke-face group (0.159 AE 0.14) was significantly higher compared to doll-face Persians (0.015 AE 0.01; P < 0.001).Conclusion and Clinical Relevance: High grades of brachycephaly are also associated with malformations of the calvarial and facial bones as well as dental malformations. As these dysmorphologies can affect animal welfare, the selection for extreme forms of brachycephaly in Persian cats should be reconsidered.